NM_001164463.1:c.5191C>T

Variant names:

• chr2-112378125-G-A
• rs751114304
• NM_001164463.1:c.5191C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164463.1(RGPD8):​c.5191C>T​(p.Leu1731Phe) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 4)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30
• Publications: 0 publications found

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013211906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164463.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD8	NM_001164463.1	MANE Select	c.5191C>T	p.Leu1731Phe	missense	Exon 22 of 23	NP_001157935.1	O14715

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD8	ENST00000302558.8	TSL:1 MANE Select	c.5191C>T	p.Leu1731Phe	missense	Exon 22 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4771C>T	p.Leu1591Phe	missense	Exon 21 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.3154C>T	p.Leu1052Phe	missense	Exon 9 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 10 AN: 8086 Hom.: 0 Cov.: 4

Gnomad AFR AF: 0.00394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000611 AC: 1 AN: 1638 AF XY: 0.00110

Gnomad AFR exome AF: 0.00725

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000129 AC: 29 AN: 224376 Hom.: 0 Cov.: 0 AF XY: 0.000134 AC XY: 16 AN XY: 119148

African (AFR) AF: 0.00244 AC: 18 AN: 7390

American (AMR) AF: 0.000737 AC: 8 AN: 10850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6006

East Asian (EAS) AF: 0.00 AC: 0 AN: 19702

South Asian (SAS) AF: 0.00 AC: 0 AN: 27806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 872

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 129186

Other (OTH) AF: 0.000244 AC: 3 AN: 12270

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00124 AC: 10 AN: 8090 Hom.: 0 Cov.: 4 AF XY: 0.00106 AC XY: 4 AN XY: 3780

African (AFR) AF: 0.00393 AC: 9 AN: 2292

American (AMR) AF: 0.00118 AC: 1 AN: 844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 84

East Asian (EAS) AF: 0.00 AC: 0 AN: 614

South Asian (SAS) AF: 0.00 AC: 0 AN: 200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2914

Other (OTH) AF: 0.00 AC: 0 AN: 128

Alfa AF: 0.000590 Hom.: 0

ExAC AF: 0.00971 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.83		Loss of stability (P = 0.0557)
MVP		0.11
ClinPred		0.26	T
GERP RS		0.85
Varity_R		0.22
gMVP		0.080
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751114304; hg19: chr2-113135702;